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Titolo:
Chemical agents that promote chromatin compaction radiosensitize tumour cells
Autore:
Biade, S; Stobbe, CC; Boyd, JT; Chapman, JD;
Indirizzi:
Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA Fox Chase Canc Ctr Philadelphia PA USA 19111 , Philadelphia, PA 19111 USA Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA Fox Chase Canc Ctr Philadelphia PA USA 19111 , Philadelphia, PA 19111 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
fascicolo: 10, volume: 77, anno: 2001,
pagine: 1033 - 1042
SICI:
0955-3002(200110)77:10<1033:CATPCC>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHINESE-HAMSTER CELLS; DOUBLE-STRAND BREAKS; CHROMOSOME CONDENSATION; OKADAIC ACID; X-RAYS; INTRINSIC RADIOSENSITIVITY; H3 PHOSPHORYLATION; IONIZING-RADIATION; PROTEIN COMPLEXES; TOPOISOMERASE-II;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Chapman, JD Fox Chase Canc Ctr, Dept Radiat Oncol, 7701 Burholme Ave, Philadelphia, PA19111 USA Fox Chase Canc Ctr 7701 Burholme Ave Philadelphia PA USA 19111
Citazione:
S. Biade et al., "Chemical agents that promote chromatin compaction radiosensitize tumour cells", INT J RAD B, 77(10), 2001, pp. 1033-1042

Abstract

Purpose: Previous studies indicated that cells whose chromatin is naturally compacted at the time of radiation are hypersensitive to radiation-induced killing, primarily by single-hit inactivation. Some chemicals that are known to promote chromatin compaction in interphase cells are here investigated for their radiosensitizing potential,Materials and Methods: Okadaic acid (OA), a protein phosphatase inhibitor,fostriecin (FC), a topoisomerase II inhibitor and trichostatin A (TSA), a histone deacetylase inhibitor, were reported to promote chromatin compaction in mammalian cells. Asynchronous populations of HT-29 (human colon carcinoma) cells were exposed to various concentrations of OA, FC and TSA for various times before irradiation with various doses of Cs-137 gamma -rays and toxicity and radiosensitization were measured. Induced chromatin compactionwas visualized by electron microscopy (EM). Historic 1 (H1) and histone 3 (H3) phosphorylation was measured by Western blotting, whole-cell fluorescence microscopy and confocal microscopy. Results: OA and FC produced significant radiosensitization at 2 Gy after short (2 h) exposures. These chemical treatments also produced increased phosphorylation of HS and increased chromatin compaction as measured by EM. A 2-h exposure of cells to TSA had no effect on cell radiosensitivity, histone phosphorylation or chromatin condensation. However, a 16-h exposure to TSA produced significant radiosensitization, histone phosphorylation and chromatin condensation, presumably by secondary mechanisms. Conclusions: These data are consistent with the hypothesis that compacted chromatin is a hypersensitive target for radiation killing. Furthermore, the modulation of chromatin conformation by drugs selectively in tumour cellsmight radiosensitize tumours whose cells are intrinsically radioresistant.

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Documento generato il 05/04/20 alle ore 04:06:48